Published online Jan 7, 2023. doi: 10.3748/wjg.v29.i1.171
Peer-review started: September 7, 2022
First decision: October 19, 2022
Revised: November 1, 2022
Accepted: December 5, 2022
Article in press: December 5, 2022
Published online: January 7, 2023
Processing time: 118 Days and 22.4 Hours
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a severe threat to human health. Polygonum multiflorum (PM) has been proven to remedy mitochondria and relieve MAFLD, but the main pharmacodynamic ingredients for mitigating MAFLD remain unclear.
To research the active ingredients of PM adjusting mitochondria to relieve high-fat diet (HFD)-induced MAFLD in rats.
Fat emulsion-induced L02 adipocyte model and HFD-induced MAFLD rat model were used to investigate the anti-MAFLD ability of PM and explore their action mechanisms. The adipocyte model was also applied to evaluate the activities of PM-derived constituents in liver mitochondria from HFD-fed rats (mitochondrial pharmacology). PM-derived constituents in liver mitochondria were confirmed by ultra-high-performance liquid chromatography/mass spectrometry (mitocho
PM repaired mitochondrial ultrastructure and prevented oxidative stress and energy production disorder of liver mitochondria to mitigate fat emulsion-induced cellular steatosis and HFD-induced MAFLD. PM-derived constituents that entered the liver mitochondria inhibited oxidative stress damage and improved energy production against cellular steatosis. Eight chemicals were found in the liver mitochondria of PM-administrated rats. The anti-steatosis ability of one monomer and the anti-MAFLD activity of the monomer group were validated.
PM restored mitochondrial structure and function and alleviated MAFLD, which may be associated with the remedy of oxidative stress and energy production. The identified eight chemicals may be the main bioactive ingredients in PM that adjusted mitochondria to prevent MAFLD. Thus, PM provides a new approach to prevent MAFLD-related mitochondrial dysfunction. Mitochondrial pharmacology and pharmacochemistry further showed efficient strategies for determining the bioactive ingredients of Chinese medicines that adjust mitochondria to prevent diseases.
Core Tip: We found that Polygonum multiflorum (PM) protected the mitochondrial ultrastructure and prevented oxidative stress and energy production disorder in the liver mitochondria to mitigate metabolic dysfunction-associated fatty liver disease (MAFLD). Eight chemicals were identified from the liver mitochondria of the PM-treated rats using a novel strategy based on mitochondrial pharmacology and pharmacochemistry. The constituents identified regulated mitochondria to alleviate MAFLD. Our results indicate that PM restored mitochondrial structure and function and alleviated MAFLD, which may be related to oxidative stress and energy production. The eight substances may be the main pharmacodynamic ingredients in PM that regulate mitochondria to prevent MAFLD.